Computational Study on the Molecular Inclusion of Indomethacin by β- Cyclodextrin for Improving Its Bioavailability

Indomethacin (indo) is an effective non-steroidal anti-inflammatory drug. Yet its poor water solubility affects its bioavailability inside human body. To enhance the bioavailability of indo, inclusion complexation has been applied to modify the physical and chemical properties of the drug. However, no computational study concerning the stability of inclusion complexes formed between indo and β – cyclodextrin (βCD) has been reported yet. In this work, the structures of indo, βCD and their inclusion complexes are calculated at Austin Model 1 (AM1) and Density Functional Theory (DFT) using the STO-3G basis set . Four inclusion complexes between indo and βCD have been constructed and their relative stability is reported. Atoms-in-Molecules (AIM) analyses based on the B3LYP/cc-pvdz wave function are used to verify the existence of the intermolecular hydrogen bonds. It was found that the most stable complex among the four inclusion complexes was the one formed with the inclusion of methoxy phenyl moiety of indo and βCD at 1:1 ratio. Our pioneer study provided valuable information about the inclusion mechanisms and dynamics of indo and βCD in order to enhance the bioavailability of the drug